DNA Collisions Lead to Higher Mutation Rates

DNA duplicates itself in a process called replication. In another process, translation, the genetic code is read and used to produce the proper proteins. These two events can occur simultaneously in a cell. The cellular machinery required for these processes follows along the same DNA strand, occasionally leading to collisions. In a recent paper published in Nature, researchers analyzed the consequences of these DNA collisions. They found that collisions can trigger mutations, leading to genetic changes and diseases.

Researchers from the Baylor College of Medicine and the University of Wisconsin developed a laboratory assay that made it possible to track mutations in a bacterial gene. They used the bacteria Bacillus subtilis and introduced a gene that caused the DNA machinery to run in the same direction, preventing collisions. In a different group, the researchers introduced the gene in a way that forced them to collide.

In the bacteria engineered to have replication-translation collisions, mutation rates were significantly higher. Most of these mutations were insertions, deletions, or substitutions. Substitution mutations are point mutations in which a single nucleotide is swapped for another, potentially resulting in the wrong protein. Insertions and deletions can be far more serious. They can lead to what is called a frameshift mutation, in which an additional or deleted nucleotide causes the entire DNA reading frame to shift. This can cause a number of proteins to change. In addition, the researchers found that most of these mutations occurred in the promoter region of the gene. This region is normally responsible for regulating gene expression.

The researchers concluded that replication-transcription collisions lead to higher mutation rates. Mutations can lead to disease, such as cancer, but they’re also the driving force behind evolution. These new findings can help us understand how these mutations occur and potentially help us cure genetic disorders.

REFERENCE

Sabari Sankar et al. The nature of mutations induced by replication–transcription collisions. Nature (2016).

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